A complete understanding of the cellular processes leading to nerve regeneration, ranging from the recruitment of quiescent catabolic machinery to the re-innervation of proper target structures, requires analysis at the molecular level. My proposed research will focus on changes in gene expression relevant to regeneration of the sciatic nerve in mice. Changes in the cell body occurring as a response to injury during PNS regeneration are mimicked in the CNS when an appropriate environment is experimentally provided to support regeneration. Thereby, the sciatic nerve model system will help in our understanding of both PNS and CNS regeneration. In addition, this model system is ideal for the study of pain mechanisms and the maladaptive response to injury. The response of the injured PNS has been compared to the processes occurring during development. Therefore, this model could identify genes that are similarly regulated during development and regeneration. The first step of the proposed research involves the identification of genes whose expression is altered with injury to the sciatic nerve through the use of new expression profiling technology. As a second step, we will characterize the spatial and temporal expression of these genes at different developmental stages and after injury. Third, functional studies of the contribution of these genes to the regeneration process will be conducted. The ultimate O(1.71 n1 goal of this work is to obtain valuable knowledge that can be applied to therapeutic procedures for CNS injury.
